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Scientists have combined functional and computational analysis to predict the substrate specificity of a family of glycosyltransferases from Arabidopsis thaliana, creating a tool that enables researchers to classify the donor and acceptor specificity of glycosyltransferase enzymes.
A structural study supported by molecular dynamics simulations describes the basis of receptor-subtype selectivity of a small-molecule antagonist of the human muscarinic M2 receptor.
Bioinformatic analysis coupled to substrate-reactivity profiling for the glycosyltransferase (GT) enzyme superfamily supports the development of ‘GT-Predict’ as a tool for functional prediction of GT–substrate relationships.
High-throughput screening and activity-based protein profiling find a selective and in vivo–active inhibitor of the membrane-associated serine hydrolase ABHD12 that alters lysophospholipid content and has immunostimulatory effects.
HIP1R directly interacts with PD-L1 and targets PD-L1 for lysosomal degradation. Development of a rationally designed peptide incorporating the PD-L1 binding sequence of HIP1R with a lysosomal targeting sequence promotes PD-L1 degradation.
The use of an allosteric drug-design method resulted in the identification of a first-in-class cellularly active SIRT6 activator that induces cell-cycle arrest in the G0–G1 phase, thus suppressing proliferation in human hepatocellular carcinoma cells.
Structural and biochemical analysis of propionyl-CoA synthase reveals that it forms a reaction chamber containing three active sites, which sequesters the reactive intermediate acrylyl-CoA during the conversion of 3-hydroxypropionate to propionyl-CoA.
An inhibitor of the YEATS domain was developed by targeting a unique π-π-π stacking in the YEATS–Kcr recognition. An ENL YEATS-selective inhibitor, XL-13m, helps probe the YEATS-dependent role of ENL in the leukemogenic transcription program.
The proteome-wide application of a probe that selectively labels cysteine residues oxidized to the sulfinic acid form reveals the mammalian S-sulfinylome and uncovers novel substrates of the sulfinyl reductase sulfiredoxin, opening yet unexplored realms of cysteine-based redox regulation.
Engineering of small-molecule-responsive RNA-binding proteins enables chemical regulation of modified mRNA or RNA replicon expression within mammalian cells for applications in synthetic circuit design and RNA-centered therapeutics.
The active-state structure of a GPCR occupied by a partial agonist, β2AR with salmeterol, together with mutagenesis and biophysical studies, explains this ligand's unusual pharmacological profile.
In response to the deletion of key genes involved in biosynthesis of the essential CoA precursor β-alanine, Escherichia coli overcomes this pathway damage by successively evolving alternative metabolic pathways.
mmBCFAs are endogenous fatty acids synthesized from BCAAs by brown and white adipose tissue via CrAT and FASN promiscuity. BCAA catabolism and mmBCFA lipogenesis are decreased by obesity-induced adipose hypoxia and influenced by the microbiome.
Current drug discovery efforts focus on proteins because of their ability to form stable, structured pockets. A recent study demonstrates that targeting stable, structured bioactive RNA motifs, such as autocatalytic introns, may provide a novel method of expanding druggability and selectivity.
A Donnan equilibrium causes an influx of chloride ions into the Escherichia coli periplasm when the bacterium finds itself in gastric fluid. The combination of low pH and high anion concentration drives proteins to aggregate, a potentially lethal event unless prevented by specific chaperones.
Protonation of periplasmic protein carboxylic groups creates a Donnan equilibrium in the bacterial periplasmic space at low pH, leading to accumulation of Cl− and unfolding and aggregation of periplasmic proteins, which can be rescued by chaperones.
